The overall objectives of this proposal are to study: 1) the use of current and development of new assay methods for erythropoietin (Epo) studies; 2) identification of the site of production of erythropoietin; 3) assessment of the role of hematopoietic control mechanisms in pregnancy, uremia and cyclic hematopoiesis. Studies have shown that a highly significant correlation exists when the titers of erythroid factors as measured with a standard erythrocythemic mouse assay are compared with those obtained in vitro with a fetal mouse liver cell assay although the latter are usually somewhat higher. Studies on the in vitro production of Epo in tissue culture showed that it was possible to produce almost routinely small quantities of Epo but that there was no discernable relationship between the production of erythropoietin, thrombopoietin and erythrogenin, or erythropoietin and erythrogenin, suggesting that these substances all represent distinct entities. Studies have continued using cyclic hematopoietic dogs. Diffusion chamber studies demonstrated that the bone marrow of these dogs have a normal proliferative ability during periods of neutropenia but a decreased ability during the period of neutrophilia. The results of studies in dehydrated mice as a model for the anemia of space flight suggested that factors outside of the normal erythropoietic control pathway (such as energy balance) may cause this syndrome.